1. Field of the Invention
The present invention relates to a tricyclic triazolobenzazepine derivative having antiallergic activity as a prodrug, an intermediate for synthesizing the same, a process for producing the same, and an antiallergic agent.
2. Background Art
In recent years, it has been revealed that allergic reactions induced by various stimuli such as immunoreactions can be divided into two reactions, i.e., an immediate reaction which occurs immediately after the stimulation and a delayed reaction which occurs several hours after the stimulation (see, for example, “Laie Asthmatic Responses”, P. M. O'byrne, J. Dolovich and F. E. Hargreave, Am. Rev. Respir. Dis., 1987; 136: 740–751). Especially, the control of the latter reaction has become important.
Clinical studies show that there are few drugs which are significantly effective in inhibiting the delayed allergic reaction. Thus, the development of drugs therapeutically effective in treating both the immediate reaction and the delayed reaction has been expected in the art.
Sodium cromoglicate has been known as a representative drug for inhibiting the immediate and delayed allergic reactions. This drug is clinically administered by inhalation because it is not useful when orally administered.
The administration by inhalation, however, is disadvantageous in that it is difficult to properly administer the drug to babies, infants, and children and that it is difficult to continuously administer the drug to patients who are highly sensitive to inhalation stimuli.
Thus the development of oral drugs which can inhibit both the immediate and delayed allergic reactions and have excellent efficacy have been expected in the art.
In recent years, many studies on antiallergic agents and therapeutic agents for asthma have been conducted in the art. Tricyclic compounds containing seven membered ring which have been studied include dibenzoxepine derivatives (Japanese Patent Laid-Open Nos. 10784/1988 and 78292/1993 and Journal of Chemical & Pharmaceutical Bulletin, vol. 39, No. 10, p. 2724 and p. 2729 (1991)), dibenzoxazepine derivatives (Japanese Patent Laid-Open Nos. 184963/1991, 211071/1992, and 65257/1993 and EP 5180720), and dibenzocycloheptene derivatives (WO 93/13068). Further, tricyclic benzazepine derivatives and tricyclic benzothiazepine derivatives are disclosed in EP 0686636, WO 95/18130, and WO 97/00258.
Meanwhile, a prodrug technique has been known as one means for improving the bioavailabilitv of a drug (Keiko Toyo Seizai No Sekkei To Hyoka (Design and Assay of Oral Preparation): edited by Mitsuru Hashida, Yakugyo Jiho Co., Ltd., pp. 216–231 (1995)). Chemical modification of a carboxyl, hydroxyl, amino or other group of the drug through an ester, amido, acetal or other bond can improve the bioavailability of the drug. However, any 1,2,3-triazole-modified prodrug has not been reported in the art.